This collaborative program involves investigators from Departments of Biomedical Engineering and Radiology at Washington University in St. Louis. The ultimate goal of this work is to develop and validate Au nanocages with targeting ligands as a novel class of therapeutic agents, which can serve as nanoscale transducers to effectively convert NIR light into heat and selectively kill cancer cells without any adverse side effects. The scope of this research includes: i) developing robust methods for large-scale production of Au nanocages with controlled size, wall thickness, absorption cross section, and surface functionality;ii) understanding the in vitro targeting capability and the role of Au nanocages in photothermal destruction of cancer cells;iii) assessing the biodistribution of PEGylated Au nanocages and maximizing their capability for passive targeting of tumor in an animal model;iv) developing Au nanocages with the right size and surface chemistry for a combination of passive and active tumor targeting in an animal model;and v) validating and optimizing the use of functionalized Au nanocages for photothermal destruction of tumor in an animal model. If successful, the technology to be developed in this application will provide a highly effective and selective method for cancer treatment. By varying the ratio of absorption to scattering cross section, the functionalized Au nanocages could also serve as molecular contrast agents for a number of imaging modalities, including optical coherence tomography (OCT), photoacoustic tomography (PAT), two-photon fluorescence, as well as CT (because Au is also a strong absorber of X-ray). As a result, Au nanocages have the potential to become a novel class of dual agents for both diagnostic and therapeutic applications PUBLIC HEALTH RELEVANCE: The ultimate goal of this work is to develop and validate gold nanocages with targeting ligands as a novel class of therapeutic agents, which can serve as nanoscale transducers to effectively convert NIR light into heat and selectively kill cancer cells without any adverse side effects. If successful, the technology to be developed in this application will provide a highly effective and selective method for cancer treatment. By varying the ratio of absorption to scattering cross section, the gold nanocages could also serve as molecular contrast agents for a number of imaging modalities, including optical coherence tomography, photoacoustic tomography, two-photon fluorescence, as well as computed tomography (because gold is also a strong absorber of X-ray). To this end, gold nanocages have the potential to become a novel class of dual agents for both diagnostic and therapeutic applications.